Cancer Therapy

You have full text access to this OnlineOpen article

Sustained delivery and efficacy of polymeric nanoparticles containing osteopontin and bone sialoprotein antisenses in rats with breast cancer bone metastasis

  1. Victoria Elazar1,
  2. Hassan Adwan2,
  3. Tobias Bäuerle2,
  4. Keren Rohekar1,
  5. Gershon Golomb1,†,*,
  6. Martin R. Berger2

Article first published online: 8 SEP 2009

DOI: 10.1002/ijc.24890

Issue

International Journal of Cancer

International Journal of Cancer

Volume 126, Issue 7, pages 1749–1760, 1 April 2010

Additional Information

How to Cite

Elazar, V., Adwan, H., Bäuerle, T., Rohekar, K., Golomb, G. and Berger, M. R. (2010), Sustained delivery and efficacy of polymeric nanoparticles containing osteopontin and bone sialoprotein antisenses in rats with breast cancer bone metastasis. Int. J. Cancer, 126: 1749–1760. doi: 10.1002/ijc.24890

Author Information

  1. 1

    Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel

  2. 2

    Unit of Chemotherapy and Toxicology, German Cancer Research Center, Heidelberg, Germany

  1. †

    Fax: +972-2-6757126

*Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, 12065 Ein Kerem, Jerusalem 91120, Israel

  1. †

    Fax: +972-2-6757126

Publication History

  1. Issue published online: 28 JAN 2010
  2. Article first published online: 8 SEP 2009
  3. Manuscript Accepted: 27 AUG 2009
  4. Manuscript Received: 21 MAY 2009

Funded by

  • German-Israeli Cooperation in Cancer Research, DKFZ (Germany), and The Ministry of Science (Israel). Grant Number: CA 114/1984
  • BMBF BioDisc Cooperation (DKFZ-MOS). Grant Number: 0315014/G401

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (511K)

Keywords:

  • antisense;
  • nanoparticles;
  • non-viral delivery;
  • bone metastasis;
  • mammary carcinoma

Abstract

Poor prognosis in mammary carcinoma is associated with a certain expression profile of a defined set of genes including osteopontin and bone sialoprotein. Efficient and specific delivery of antisenses (AS) and a protection of the sequences from degradation are the crucial conditions for AS therapeutic efficiency. We hypothesized that effective and safe AS delivery direceted against these genes could be achieved by polymeric nanoparticles (NP) fabricated from a biocompatible polymer. Due to their nano-size range and small negative charge, AS-NP can overcome the absorption barrier offering increased resistance to nuclease degradation, sustained duration of AS administration, and consequently, prolonged antisense action. The ASs designed against OPN and BSP-II were successfully encapsulated in NP composed of the biodegradable and biocompatible polylactide-co-glycolide polymer (PLGA), exhibiting sustained release and stability of the ASs. The therapeutic efficacy of the AS-NP delivery system was examined in vitro, and in a breast cancer bone metastasis animal model of MDA-MB-231 human breast cancer cells in nude rats. Treatment with OPN-AS or BSP-AS loaded NP in comparison with osmotic mini-pumps (locoregional injection and SC implants, respectively) resulted in a significant decrease in both, tumor bone metastasis incidence and in the size of the lesions in rats with metastases. Despite its smaller dose, AS-NP exhibited a better therapeutic efficacy than osmotic mini-pumps in terms of lesion ratio at later time periods (8–12 weeks). It may be concluded that AS delivery by NP is a promising therapeutic modality providing stability of the encapsulated AS and a sustained release.

View Full Article (HTML) Get PDF (511K)